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Fumarate
Kinds of Fumarate Terms modified by Fumarate Selected AbstractsComparative Study of Clinical Efficacy and Tolerance in Seasonal Allergic Conjunctivitis Management with 0.1% Olopatadine Hydrochloride versus 0.05% Ketotifen FumarateACTA OPHTHALMOLOGICA, Issue 2000Alejandro J. Aguilar ABSTRACT. Objective: To compare the clinical efficacy and tolerance of 0.1% olopatadine hydrochloride (OHC) versus 0.05% ketotifen fumarate (KF) in the management of allergic conjunctivitis. Materials and Methods: Eighty adult patients with a history of allergy (allergic conjunctivitis, hay fever, asthmatic bronchitis and dermatitis) that were showing allergic conjunctivitis signs and symptoms (itching, hyperemia, mucous discharge and tearing) at the time of inclusion in this study were evaluated. Patients were divided in two groups, A and B. Group A patients were treated with OHC and group B patients were treated with KF. Both groups received one drop in the affected eye every 12 hrs. The start time of this study was the first patient visit, in which the medication was instilled for the first time. Both groups of patients were evaluated 30 min, 48 hr., 7 days and 14 days later. Local tolerance of each medication was evaluated. Results: Clinical improvement of the signs and symptoms of allergic conjunctivitis occurred in 42.5% to 62.5% of the patients in Group A when assessed 30 min following the first topical ocular dose of olopatadine. However, mucous discharge was not affected. Forty-eight (48) hrs. after the first instillation, improvements in 57.5% to 75% of the patients were shown in every evaluated parameter. After 7 days of treatment, positive clinical results were observed in 80% to 87.5% of the treated patients. Except for the patients that were dismissed from the study before the seventh day of treatment due to the absence of therapeutic response (4/40), all patients satisfactorily completed the therapeutic plan by the seventh day. No intolerance reactions were observed in patients of this group. In Group B patients (KF), clinical improvement of the signs and symptoms measured in the study was shown in 20.0% to 47.5% 30 min after instillation. As observed with olopatadine, no improvement in the number of patients showing mucous discharge was noted at the 30-min time point. At 48 hr. after the first instillation, 27.5% to 48% of patients showed improvement in every evaluated parameter. After 7 days of treatment, improvement was observed in 60% to 75% of patients. On Day 14, positive responses were observed in 67.5% to 75% of patients. Seventeen and one-half percent of the patients were dismissed from the study before the seventh day of treatment due to the absence of a therapeutic response. Approximately 23% of the patients had mild reactions of intolerance (stinging) which was not a cause to discontinue the treatment. Conclusion: Olopatadine hydrochloride controlled allergic conjunctivitis symptoms and signs more rapidly and to a greater extent than ketotifen fumarate. Fewer cases of treatment failure were noted with OHC, and no local intolerance reactions were observed, while KF triggered mild reactions (stinging) in 23% of patients. [source] Shoe contact dermatitis from dimethyl fumarate: clinical manifestations, patch test results, chemical analysis, and source of exposureCONTACT DERMATITIS, Issue 5 2009Ana Giménez-Arnau Background: The methyl ester form of fumaric acid named dimethyl fumarate (DMF) is an effective mould-growth inhibitor. Its irritating and sensitizing properties were demonstrated in animal models. Recently, DMF has been identified as responsible for furniture contact dermatitis in Europe. Objective: To describe the clinical manifestations, patch test results, shoe chemical analysis, and source of exposure to DMF-induced shoe contact dermatitis. Patients, Materials, and Methods: Patients with suspected shoe contact dermatitis were studied in compliance with the Declaration of Helsinki. Patch test results obtained with their own shoe and the European baseline series, acrylates and fumaric acid esters (FAE), were recorded according to international guidelines. The content of DMF in shoes was analysed with gas chromatography and mass spectrometry. Results: Acute, immediate irritant contact dermatitis and non-immunological contact urticaria were observed in eight adults and two children, respectively. All the adult patients studied developed a delayed sensitization demonstrated by a positive patch testing to DMF , 0.1% in pet. Cross-reactivity with other FAEs and acrylates was observed. At least 12 different shoe brands were investigated. The chemical analysis from the available shoes showed the presence of DMF. Conclusion: DMF in shoes was responsible for severe contact dermatitis. Global preventive measures for avoiding contact with DMF are necessary. [source] Manganese speciation in human cerebrospinal fluid using CZE coupled to inductively coupled plasma MSELECTROPHORESIS, Issue 9 2007Bernhard Michalke Dr. Abstract The neurotoxic effects of manganese (Mn) at elevated concentrations are well known. This raises the question, which of the Mn species can cross neural barriers and appear in cerebrospinal fluid (CSF). CSF is the last matrix in a living human organism available for analysis before a compound reaches the brain cells and therefore it is assumed to reflect best the internal exposure of brain tissue to Mn species. A previously developed CE method was modified for separation of albumin, histidine, tyrosine, cystine, fumarate, malate, inorganic Mn, oxalacetate, ,-keto-glutarate, nicotinamide-dinucleotide (NAD), citrate, adenosine, glutathione, and glutamine. These compounds are supposed in the literature to act as potential Mn carriers. In a first attempt, these compounds were analyzed by CZE-UV to check whether they are present in CSF. The CZE-UV method was simpler than the coupled CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-MS method and it was therefore chosen to obtain a first overview information. In a second step, the coupled method (CZE-ICP-DRC-MS) was used to analyze, in detail, which of the compounds found in CSF by CZE-UV were actually bound to Mn. Finally, 13 Mn species were monitored in CSF samples, most of them being identified: Mn-histidine, Mn-fumarate, Mn-malate, inorganic Mn, Mn-oxalacetate, Mn-,-keto glutarate, Mn-carrying NAD, Mn-citrate and Mn-adenosine. By far the most abundant Mn species was Mn-citrate showing a concentration of 0.7,±,0.13,µg,Mn/L. Interestingly, several other Mn species can be related to the citric acid cycle. [source] Reduction of fumarate, mesaconate and crotonate by Mfr, a novel oxygen-regulated periplasmic reductase in Campylobacter jejuniENVIRONMENTAL MICROBIOLOGY, Issue 3 2010Edward Guccione Summary Methylmenaquinol : fumarate reductase (Mfr) is a newly recognized type of fumarate reductase present in some ,-proteobacteria, where the active site subunit (MfrA) is localized in the periplasm, but for which a physiological role has not been identified. We show that the Campylobacter jejuni mfrABE operon is transcribed from a single promoter, with the mfrA gene preceded by a small open reading-frame (mfrX) encoding a C. jejuni -specific polypeptide of unknown function. The growth characteristics and enzyme activities of mutants in the mfrA and menaquinol : fumarate reductase A (frdA) genes show that the cytoplasmic facing Frd enzyme is the major fumarate reductase under oxygen limitation. The Mfr enzyme is shown to be necessary for maximal rates of growth by fumarate respiration and rates of fumarate reduction in intact cells measured by both viologen assays and 1H-NMR were slower in an mfrA mutant. As periplasmic fumarate reduction does not require fumarate/succinate antiport, Mfr may allow more efficient adaptation to fumarate-dependent growth. However, a further rationale for the periplasmic location of Mfr is suggested by the observation that the enzyme also reduces the fumarate analogues mesaconate and crotonate; fermentation products of anaerobes with which C. jejuni shares its gut environment, that are unable to be transported into the cell. Both MfrA and MfrB subunits were localized in the periplasm by immunoblotting and 2D-gel electrophoresis, but an mfrE mutant accumulated unprocessed MfrA in the cytoplasm, suggesting a preassembled MfrABE holoenzyme has to be recognized by the TAT system for translocation to occur. Gene expression studies in chemostat cultures following an aerobic-anaerobic shift showed that mfrA is highly upregulated by oxygen limitation, as would be experienced in vivo. Our results indicate that in addition to a role in fumarate respiration, Mfr allows C. jejuni to reduce analogous substrates specifically present in the host gut environment. [source] Hexaazamacrocycle Containing Pyridine and Its Dicopper Complex as Receptors for Dicarboxylate AnionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 22 2005Feng Li Abstract The host,guest binding interactions of the hexaazamacrocycle [26]py2N4, in its tetraprotonated form H4[26]py2N44+ as well as in its dicopper(II) complex [Cu2([26]py2N4)(H2O)4]4+, with dicarboxylate anions of different stereoelectronicrequirements, such as oxalate (ox2,), malonate (mal2,), succinate (suc2,), fumarate (fu2,) and maleate (ma2,), were evaluated. The association constants were determined using potentiometric methods in aqueous solution, at 298.0 K and 0.10 mol·dm,3 KCl. These values for the tetraprotonated ditopic receptor with the dicarboxylate anions revealed that the main species in solution corresponds to the formation of {H4[26]py2N4(A)}2+ (pH , 4,9), A being the substrate anion. The values determined are not especially high, but the receptor exhibits selectivity for the malonate anion. The study of the cascade complexes revealed several species in solution, involving mononuclear and dinuclear complexes, mainly protonated and hydrolysed species, as well as the expected complexes [Cu2([26]py2N4)(A)(H2O)x]2+ or [Cu2([26]py2N4)(A)2(H2O)y]. Ox2, and mal2, form cascade complexes with only one anion, which will necessarily bridge the two copper atoms because of the symmetrical arrangement of the dinuclear complex. The two other studied anions, suc2, and ma2,, form species involving two substrate anions, although species with only one suc2, anion were also found. UV/Vis and EPR spectroscopy have shown that the dicopper complex can operate as a sensor to detect and quantitatively determine oxalate spectrophotometrically because of the red shift of the maximum of the visible band observed by addition of ox2, to an aqueous solution of the dinuclear copper complex. However the selectivity of [Cu2([26]py2N4)(H2O)4]4+ as a receptor for ox2, in the studied series is not sufficiently high to detect ox2, spectrophotometrically in the presence of the other anions. Molecular dynamics simulations indicated that the H4[26]py2N44+ receptor provides a large and flexible cavity to accommodate the studied anions. Molecular recognition is based in electrostatic interactions rather than in multiple hydrogen-bonding interactions acting cooperatively. By contrast, the [Cu2([26]py2N4)]4+ receptor has a well-shaped cavity with adequate size to uptake these anions as bridging ligands with formation of four Cu,O bonds. The ox2, anion is encapsulated within the cascade complex while the remaining anions are located above the N6 macrocyclic plane, suggesting a selective coordination behaviour of this receptor. In spite of our molecular simulation being carried out in gas phase, the modelling results are consistent with the solution studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Kinetic Studies of the Oxidative Addition and Transmetallation Steps Involved in the Cross-Coupling of Alkynyl Stannanes with Aryl Iodides Catalysed by ,2 -(Dimethyl fumarate)(iminophosphane)palladium(0) ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 4 2004Bruno Crociani Abstract The complexes [Pd(,2 -dmfu)(P,N)] {dmfu = dimethyl fumarate; P,N = 2-(PPh2)C6H4,1-CH=NR, R = C6H4OMe-4 (1a), CHMe2 (2a), C6H3Me2 -2,6 (3a), C6H3(CHMe2)2 -2,6 (4a)} undergo dynamic processes in solution which consist of a P,N ligand site exchange through initial rupture of the Pd,N bond at lower energy and an olefin dissociation-association at higher energy. According to equilibrium constant values for olefin replacement, the complex [Pd(,2 -fn)(P,N)] (fn = fumaronitrile, 1b) has a greater thermodynamic stability than its dmfu analogue 1a. The kinetics of the oxidative addition of ArI (Ar = C6H4CF3 -4) to 1a and 2a lead to the products [PdI(Ar)(P,N)] (1c, 2c) and obey the rate law, kobs = k1A + k2A[ArI]. The k1A step involves oxidative addition to a reactive species [Pd(solvent)(P,N)] formed from dmfu dissociation. The k2A step is better interpreted in terms of oxidative addition to a species [Pd(,2 -dmfu)(solvent)(,1 -P,N)] formed in a pre-equilibrium step from Pd,N bond breaking. The complexes 1c and 2c react with PhC,CSnBu3 in the presence of an activated olefin (ol = dmfu, fn) to yield the palladium(0) derivatives [Pd(,2 -ol)(P,N)] along with ISnBu3 and PhC,CAr. The kinetics of the transmetallation step, which is rate-determining for the overall reaction, obey the rate law: kobs = k2T[PhC,CSnBu3]. The k2T values are markedly enhanced in more polar solvents such as CH3CN and DMF. The solvent effect and the activation parameters suggest an associative SE2 mechanism with substantial charge separation in the transition state. The kinetic data of the above reactions in various solvents indicate that, for the cross-coupling of PhC,CSnBu3 with ArI catalysed by 1a or 2a, the rate-determining step is represented by the oxidative addition and that CH3CN is the solvent in which the highest rates are observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection,HEPATOLOGY, Issue 6 2004Florian van Bömmel Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 105 copies/mL in contrast to 100% of the tenofovir-treated patients (P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection. (HEPATOLOGY 2004;40:1421,1425.) [source] Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine?HIV MEDICINE, Issue 7 2009C Foster Objectives Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. Methods We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic. Results In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. Conclusions The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required. [source] Long-term outcome of tenofovir disoproxil fumarate use against hepatitis B in an HIV-coinfected cohortHIV MEDICINE, Issue 5 2009G Alvarez-Uria Objectives Tenofovir disoproxil fumarate (TDF) is active against hepatitis B virus (HBV) and HIV. However, the long-term efficacy of tenofovir disoproxil fumarate (TDF) is not well known and the appearance of resistance is a major concern. We have studied the efficacy of TDF against HBV in patients treated at an Infectious Diseases Unit. Methods We carried out a retrospective observational study of the efficacy of TDF against HBV replication in a cohort of 52 HIV-coinfected patients who received TDF for at least 6 months. Results The median duration of follow-up of TDF treatment was 34 months. Forty-one patients (79%) were positive for HBV envelope antigen (HBeAg) and 35 had received previous lamivudine monotherapy for a median duration of 32 months. Virological breakthrough was observed in nine cases (17%). At the end of the follow-up period, HBV DNA levels were <1000 copies/mL in 42 patients (81%) and <200 copies/mL in 31 patients (60%). There were no significant differences between the lamivudine-naïve and lamivudine-experienced groups. In the lamivudine-experienced group, the duration of previous lamivudine monotherapy was associated with failure to achieve HBV DNA levels <200 copies/mL (P=0.036). Adding lamivudine or emtricitabine to TDF did not improve virological suppression. In 39 patients who achieved <200 HBV DNA copies/mL during TDF treatment, virological breakthrough was seen only in two patients (5%) after a median follow-up duration of 39.7 months. Conclusions TDF was able to control HBV replication in most HIV-coinfected patients after a median follow-up duration of 34 months, regardless of previous lamivudine treatment. However, a sizeable proportion of patients developed virological breakthrough. [source] Estimating renal function in patients on tenofovir disoproxil fumarate: suggestions for safer useHIV MEDICINE, Issue 7 2006J Winston No abstract is available for this article. [source] Safety and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double-blind, placebo-controlled studiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010Didier Meulien Abstract Introduction Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication. Methods The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment. Results The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR. Conclusions The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd. [source] Lack of effects between rupatadine 10,mg and placebo on actual driving performance of healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2007Eric Vuurman Abstract Introduction Rupatadine fumarate is a potent, selective, histamine H1 -receptor antagonist and PAF inhibitor with demonstrated efficacy for the relief of allergic rhinitis. Rupatadine does not easily cross the blood,brain barrier and is believed to be non-sedating at therapeutic doses. Consequently, rupatadine should show no impairment on car driving. Objective This study compared the acute effects of rupatadine, relative to placebo and hydroxyzine (as an active control), on healthy subjects' driving performance. Methods Twenty subjects received a single dose of rupatadine 10,mg, hydroxyzine 50,mg, or placebo in each period of this randomized, double-blind, three-way crossover study. Two hours postdosing, subjects operated a specially instrumented vehicle in tests designed to measure their driving ability. Before and after the driving tests ratings of sedation were recorded. Results There was no significant difference between rupatadine and placebo in the primary outcome variable: standard deviation of lateral position (SDLP); however, hydroxyzine treatment significantly increased SDLP (p,<,0.001 for both comparisons). Objective (Stanford sleepiness scale) and subjective sedation ratings (Visual Analogue Scales) showed similar results: subjects reported negative effects after hydroxyzine but not after rupatadine. Conclusion Rupatadine 10,mg is not sedating and does not impair driving performance. Copyright © 2007 John Wiley & Sons, Ltd. [source] Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth,JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2003Malcolm N. Cooke Abstract A novel approach to the manufacture of biodegradable polymeric scaffolds for tissue-engineering utilizing stereolithography (SLA) is presented. SLA is a three-dimensional (3D) printing method that uses an ultraviolet laser to photo-crosslink a liquid polymer substrate. The current generation of SLA devices provide a 3D printing resolution of 0.1 mm. The experiments utilized a biodegradable resin mixture of diethyl fumarate (DEF), poly(propylene fumarate) (PPF), and a photoinitiator, bisacylphosphine oxide (BAPO). The PPF is crosslinked with the use of the SLA's UV laser (325-nm wavelength). An SLA device was retrofitted with a custom fixture build tank enclosing an elevator-driven build table. A 3D prototype model testing the manufacturing control this device provides was created in a computer-aided-design package. The resulting geometric data were used to drive the SLA process, and a DEF/PPF prototype part was successfully manufactured. These scaffolds have application in the tissue engineering of bony substrates. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 65,69, 2002 [source] The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in BangladeshJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2001D. Gilgen Aim To investigate the effect of weekly iron supplementation on anaemia and iron deficiency among adult, female tea pluckers. Method A randomized double-blind intervention trial was conducted in a tea estate in Bangladesh where a total of 280 women received either weekly iron supplementation (200 mg ferrous fumarate and 200 mg folic acid) for 24 weeks or a matching placebo. Capillary blood samples were drawn at baseline and post-trial to determine haemoglobin, haematocrit and ferritin concentration. Mean corpuscular haemoglobin concentration (MCHC) was calculated using the haemoglobin and haematocrit values. Results The mean haemoglobin concentration in the supplemented group increased by 5.52 g L,1 over the study period, on average, while ferritin values decreased by 0.33 ,g L,1. The control group showed a decrease in both mean haemoglobin (,0.24 g L,1) and ferritin (,5.32 ,g L,1). Those individuals in the supplemented group with the lowest pretrial haemoglobin and ferritin values experienced the greatest improvements post-trial, whereas nonanaemic individuals showed a decrease in both haemoglobin and ferritin concentrations. A total of 62.2% of women in the supplemented group reported feeling better and more energetic compared to 51.1% in the placebo group; 14.4% of the supplemented group and 22.7% of the control group complained about side-effects. Conclusion Weekly iron supplementation was logistically simpler and cheaper than daily supplementation but would have to be continued on a longer term basis in order to combat both anaemia and iron deficiency. [source] National survey of the prevalence and conditions of selection of HIV-1 reverse transcriptase K70E mutation,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2008C. Delaugerre Abstract Tenofovir disoproxil fumarate (TDF) has become an important component of HIV combination therapy because of its potency and once-daily dosing. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. Concomitant association of K65R and K70E was possible but infrequent (11%). At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection. J. Med. Virol. 80:762,765, 2008. © 2008 Wiley-Liss, Inc. [source] Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockadeJOURNAL OF NEUROCHEMISTRY, Issue 2 2009Eleonora Calcagno Abstract Blockade of NMDA receptors by intracortical infusion of 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) increases glutamate (GLU) and serotonin (5-HT) release in the medial prefrontal cortex and impairs attentional performance in the 5-choice serial reaction time task. These effects are prevented by the 5-HT2A receptor antagonist, (R)-(+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine methanol (M100907). We explored the roles of endogenous 5-HT and 5-HT1A and 5-HT2C receptors in the mechanisms by which M100907 suppresses CPP-induced release of cortical GLU and 5-HT using in vivo microdialysis. CPP raised extracellular GLU and 5-HT by about 250% and 170% respectively. The 5-HT synthesis inhibitor, p -chlorophenylalanine (300 mg/kg), prevented M100907 suppressing CPP-induced GLU release. The effect of M100907 on these rises of GLU and 5-HT and attentional performance deficit was mimicked by the 5-HT2C receptor agonist, (S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine fumarate, (Ro60-0175, 30 ,g/kg) while intra-mPFC (SB242084, 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline, 0.1 ,M), a 5-HT2C receptor antagonist, prevented the effect of M100907 on extracellular GLU. The 5-HT1A receptor antagonist, N -[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N -(2-pyridinyl)cyclohexane carboxenide trihydrochloride (100 ,M) abolished the effect of M100907 on the CPP-induced 5-HT release. The data show that blockade of 5-HT2A receptors is not sufficient to suppress the CPP-induced rise of extracellular GLU and 5-HT and suggest that M100907 suppresses GLU release induced by CPP by enhancing the action of endogenous 5-HT on 5-HT2C receptors. [source] Brain metabolism of exogenous pyruvateJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Susana Villa Gonzalez Abstract Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3- 13C]pyruvate led to dose-dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3- 13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4- 13C]glutamate or [2- 13C]GABA from [3- 13C]pyruvate, but reduced formation of [4- 13C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3- 13C]lactate from [2- 13C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo, but that care must be taken to avoid the seizure-inducing effect of pyruvate given in large doses. [source] Local injection of thrombin-related peptide (TP508) in PPF/PLGA microparticles,enhanced bone formation during distraction osteogenesisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2008Yan Wang Abstract We have previously demonstrated that injections of the thrombin-related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L -lactic- co -glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508-treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p,<,0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 µg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:539,546, 2008 [source] Intrinsic adhesion force of lubricants to steel surfaceJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Jonghwi Lee Abstract The intrinsic adhesion forces of lubricants and other pharmaceutical materials to a steel surface were quantitatively compared using Atomic Force Microscopy (AFM). A steel sphere was attached to the tip of an AFM cantilever, and its adhesion forces to the substrate surfaces of magnesium stearate, sodium stearyl fumarate, lactose, 4-acetamidophenol, and naproxen were measured. Surface roughness varied by an order of magnitude among the materials. However, the results clearly showed that the two lubricants had about half the intrinsic adhesion force as lactose, 4-acetamidophenol, and naproxen. Differences in the intrinsic adhesion forces of the two lubricants were insignificant. The lubricant molecules were unable to cover the steel surface during AFM measurements. Intrinsic adhesion force can slightly be modified by surface treatment and compaction, and its tip-to-tip variation was not greater than its difference between lubricants and other pharmaceutical particles. This study provides a quantitative fundamental basis for understanding adhesion related issues. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2310,2318, 2004 [source] Alterations in Brain Glucose Utilization Accompanying Elevations in Blood Ethanol and Acetate Concentrations in the RatALCOHOLISM, Issue 2 2010Robert J. Pawlosky Background:, Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Methods:, Rats were infused with solutions of sodium acetate, ethanol, or saline containing 13C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs' cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Results:, Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of 13C-glucose into the brain compared to controls and the concentration of brain 13C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg2+ in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, ,-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD+]/[NADH] was lower, the free mitochondrial [NAD+]/[NADH] and [CoQ]/[CoQH2] were oxidized and the ,G, of ATP lowered by acetate infusion from ,61.4 kJ to ,59.9 kJ/mol. Conclusions:, Animals with elevated levels of blood ethanol or acetate had decreased 13C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in 13C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in ,G, of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form. [source] Radical polymerization behavior of ethyl ortho -(4-phenyl-1,3-dioxolan-2-yl)phenyl fumarateJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 17 2002Makiko Seno Abstract The polymerization of ethyl ortho -(4-phenyl-1,3-dioxolan-2-yl)phenyl fumarate (EPDPF) with dimethyl 2,2,-azobisisobutyrate (MAIB) was kinetically investigated in benzene. The polymerization rate (Rp) at 60 °C was presented by Rp = k[MAIB]1.1[EPDPF]0.8. The number-average molecular weight of poly(EPDPF) was in the range of 2500,3500. Analysis of 1H and 13C NMR spectra of the resulting polymers suggested that the radical polymerization of EPDPF proceeds in a complicated manner involving vinyl addition, intramolecular hydrogen abstraction, and ring opening of the cyclic acetal. The polymerization system involved electron spin resonance (ESR)-observable poly(EPDPF) radicals under the practical polymerization conditions. ESR-determined apparent rate constants (2.0,8.5 L/mol s) of propagation increased with increasing initiator concentration and decreasing monomer concentration. The apparent rate constants (0.68,6.6 × l06 L/mol s) of termination decreased with the monomer concentration and slightly increased with the initiator concentration. The activation energies of initiation (Ei), propagation (Ep), and termination (Et) were calculated as Ei = 158, Ep = 41, and Et = 30 kJ/mol, respectively. Radical copolymerization of EPDPF with styrene was also examined at 70 °C in benzene. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2945,2955, 2002 [source] Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosisLIVER INTERNATIONAL, Issue 6 2008Won Hyeok Choe Abstract Background/Aims: There is no consensus on the management of patients with adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non-response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child,Pugh score and serum creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were measured in stored samples. Results: In five of six patients, ADV-resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6,21 months). The Child,Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non-response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre-existing LMV resistance. [source] Treatment of recurrent hepatitis B infection in liver transplant recipientsLIVER TRANSPLANTATION, Issue 10B 2002Norah A. Terrault MD 1Therapeutic decisions are guided by a patient's clinical status (severity of disease and presence of comorbidities) and previous drug-exposure history. 2Lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B virus (HBV) infection caused by wild-type virus or failure of hepatitis B immunoglobulin therapy. Lamivudine resistance, developing in approximately 25% after 12 months of therapy, is its main limitation. 3Famciclovir is safe in liver transplant recipients; however, virological and clinical responses are less consistent than with lamivudine. Thus, lamivudine is favored over famciclovir as first-line therapy in transplant recipients with no previous exposure to nucleoside analogues. 4Although limited in availability, adefovir dipivoxil appears safe and effective in treating liver transplant recipients with lamivudine-resistant HBV disease. Close monitoring of renal function is recommended, with dose adjustment in patients with reduced creatinine clearances. 5Limited data suggest that intravenous ganciclovir, tenofovir disoproxil fumarate, and interferon alfa may be useful as rescue therapies for patients with lamivudine- or famciclovir-resistant HBV disease. 6Antiviral therapy with two or more suitable agents may minimize the chance for viral resistance; therefore, future therapeutic strategies likely will use combination therapy in the long-term management of recurrent HBV disease. [source] Economic evaluation of BDP/formoterol fixed vs two single inhalers in asthma treatmentALLERGY, Issue 9 2010B. Brüggenjürgen To cite this article: Brüggenjürgen B, Ezzat N, Kardos P, Buhl R. Economic evaluation of BDP/formoterol fixed vs two single inhalers in asthma treatment. Allergy 2010; 65: 1108,1115. Abstract Background:, Asthma treatment costs are substantial, the largest proportion being incurred by medications. Combination therapy with inhaled corticosteroids (ICS) and long-acting beta2 -agonists (LABA) is recommended in patients not adequately controlled by ICS alone. Aim of this study was to compare costs and health outcomes of a fixed ICS,LABA combination of beclomethasone dipropionate (BDP) and formoterol fumarate (FF) vs the same drugs delivered via separate inhalers in Germany. Methods:, A cost-minimization analysis, a cost-effectiveness analysis, as well as a threshold analysis were undertaken. Efficacy results were obtained from a recent clinical trial. Cost inputs include medical costs, physician costs, and hospital admission costs. Medical costs, health outcomes, and treatment costs were also varied to assess their impact on results. Results:, Beclomethasone dipropionate/FF fixed combination was less costly compared to BDP + FF delivered as separate inhalers, costs totaling ,525 and ,637, respectively, over a 24-week treatment period. The incremental cost-effectiveness ratio was ,,9.77 per additional day free of asthma symptoms. Equal cost-effectiveness ratios would still be obtained at a price of the fixed combination increased by 3.4-fold. Conclusion:, A cost-minimization analysis as well as a cost-effectiveness analysis for Germany based on different product price calculations show that BDP/FF fixed combination is superior to BDP + FF delivered via separate inhalers. [source] Differentiation of hydatid cyst from cysticercus cyst by proton MR spectroscopyNMR IN BIOMEDICINE, Issue 5 2002Monika Garg Abstract The metabolite patterns obtained by ex vivo proton MR spectroscopy of fluid from different locations of hydatid cysts of sheep and humans (n,=,16) and cysticercus cysts of swine and humans (n,=,25) were compared with an objective of differentiating the two parasites on the basis of their metabolite pattern. The spectra from hydatid fluid differed from cysticercus cyst by the absence of creatine in the former. When the hydatid cyst was fertile, malate and/or fumarate was also observed, which was absent in cysticercus cyst. The most likely explanation for the presence of creatine only in the cysticercus fluid is its active diffusion from the surrounding host tissue along with a contribution from the musculature present in the bladder wall of the cyst. Copyright © 2002 John Wiley & Sons, Ltd. [source] Use of ferrous fumarate to fortify foods for infants and young childrenNUTRITION REVIEWS, Issue 9 2010Richard Hurrell Ferrous fumarate is currently recommended for use in the fortification of foods for infants and young children. This recommendation is based on the compound's good sensory properties and on results from isotope studies in adults that reported similar iron absorption values for ferrous fumarate and ferrous sulphate (relative bioavailability [RBV] of ferrous fumarate, 100). However, later isotope studies conducted on both iron-replete and iron-deficient young children found that iron absorption from ferrous fumarate was only about 30% of that achieved from ferrous sulphate (RBV, 30). The reasons for the differences observed in adults compared with children are unclear but could be related to the following factors: lower iron status in children resulting in greater iron absorption via upregulation from ferrous sulphate but not from ferrous fumarate; reduced gastric acid secretion in children leading to retarded dissolution of ferrous fumarate; or an influence of added ascorbic acid on RBV. Ferrous fumarate-fortified complementary foods have been demonstrated to improve iron status in iron-deficient infants and, more recently, to prevent iron deficiency equally as well as ferrous sulphate in iron-replete infants. However, current evidence indicates that iron-deficient infants and young children may absorb iron from ferrous fumarate less well than iron from ferrous sulfate and that, for equivalent efficacy, complementary foods targeted at such infants and young children should contain more iron in the form of fumarate. [source] Efficacy and safety of single- and multiple-dose ketotifen fumarate 0.025% ophthalmic solution in a pediatric populationPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2004Mark B. Abelson Allergic conjunctivitis can seriously disrupt children's daily activities. This study assessed the efficacy (onset and duration of action) and safety of ketotifen fumarate 0.025% ophthalmic solution compared with vehicle placebo in pediatric subjects after single and multiple dosing. This was a double-masked, multicenter, fellow-eye, placebo-controlled, conjunctival allergen challenge trial. Eligible subjects (8,16-yr-olds) who produced a qualifying reaction to allergen were randomized to a single dose (one drop) of ketotifen fumarate in one eye and vehicle placebo in the fellow eye, followed by an allergen challenge at 15 min and 8 h post-dose. Subjects who had a qualifying reaction to allergen in the placebo-treated eye and a qualifying response to ketotifen in the active-treated eye following the single dose were re-randomized to a multiple-dose treatment period. They were instructed to instill one drop of ketotifen fumarate in one eye and placebo in the other eye twice daily for 4 wk. An allergen challenge was conducted 8 h after the last dose. The primary efficacy assessment was ocular itching, judged by the subject at 3, 7, and 10 min post-allergen challenge after single- and multiple-dose treatments. Other ocular signs and symptoms were assessed at 7, 10, and 15 min post-dose. A total of 133 subjects were randomized to single-dose treatment; 105 were evaluable for efficacy. Of these, 60 were re-randomized to multiple-dose treatment, and 55 were evaluable for efficacy. After single and multiple doses, ketotifen fumarate significantly inhibited ocular itching compared with placebo at all post-challenge timepoints (p < 0.001) and also significantly reduced hyperemia, chemosis, and lid swelling (p = 0.031). No drug-related systemic adverse events were reported, and ocular adverse events were comparable to placebo. No subject discontinued prematurely due to an adverse event. These results indicate that ketotifen fumarate 0.025% ophthalmic solution is an effective and safe treatment option for children with allergic conjunctivitis. [source] Physiological changes in white lupin associated with variation in root-zone CO2 concentration and cluster-root P mobilizationPLANT CELL & ENVIRONMENT, Issue 10 2005M. D. CRAMER ABSTRACT White lupin (Lupinus albus L.) mobilizes insoluble soil phosphorus through exudation of organic acids from ,cluster' roots. Organic acid synthesis requires anaplerotic carbon derived from dark CO2 fixation involving PEP-carboxylase. We tested the hypothesis that variation in root-zone CO2 concentration would influence organic acid synthesis and thus P mobilization. Root-zone CO2 concentrations and soil FePO4 concentrations supplied to sand-grown white lupin (cv. Kiev Mutant) were varied. More biomass accumulated in plants supplied with 360 µL L,1 CO2 to the root-zone, compared with those aerated with either 100 or 6000 µL L,1 CO2. Increased FePO4 in the sand resulted in greater leaf P concentrations, but root-zone [CO2] did not influence leaf P concentration. Suppression of cluster-root development in plants supplied with 100 µL L,1 root-zone CO2 was correlated with increased leaf [P]. However, at both 360 and 6000 µL L,1 CO2, cluster-root development was suppressed only at the highest leaf P concentration. Phloem sap [P] was significantly increased by greater [FePO4] in the sand, but was reduced with increased root-zone [CO2], and this may have triggered increased cluster-root initiation. Succinate was the major organic acid (carboxylate) in the phloem sap (minor components included malate, citrate, fumarate) and was increased at greater [FePO4], suggesting that this shoot-derived carboxylate might provide an important source of organic acids for root metabolism. Since cluster root development was inhibited by increasing concentrations of FePO4 in the sand, it is possible that succinate was utilized for the functioning of the root-nodules. [source] Non-bond crosslinked macroporous thermally reversible hydrogels,POLYMERS FOR ADVANCED TECHNOLOGIES, Issue 9 2007Yair Avny Abstract Non-bond crosslinked macroporous thermally reversible hydrogels of poly- N -isopropylacrylamide were obtained by copolymerization with the crosslinking agent cyclic octaethylene glycol fumarate, a 29-membered ring, having a polymerizable double bond; threading of polymer chains into the macrocyclic ring being the cause for the crosslinking. These hydrogels showed a high swelling capacity in water which could be controlled by varying the molar ratio of monomer/crosslinking agent. They rapidly ,collapsed' at 33° and swelled back at low temperatures. Copyright © 2007 John Wiley & Sons, Ltd. [source] Determination of aerobic-anaerobic metabolism-related compounds in a Chaoborus flavicans population by infusion ion trap mass spectrometry of extracts of individual larvaeRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2006Maria da Graça Gama Melão In a daily migration, the aquatic larvae of Chaoborus flavicans (a phantom midge) alternate oxygen-saturated and anoxic lake strata. To investigate this cycle, larvae were collected at a natural environment, and acetate, propionate, pyruvate, lactate, glycerol, phosphate, maleate, succinate, glucose and citrate were determined. Each larva was homogenized with 200,µL water and deproteinized with a spin-filter; 50,µL aliquots were mixed with 50,µL of a buffer containing 80,mM propylamine, 20,mM HCl and 0.06,mM 2,4-dihydroxybenzoic acid (internal standard) in methanol. The extracts were infused in an electrospray ionization ion-trap mass spectrometer. The limits of detection for the [M,H], peaks ranged from 2,µM for pyruvate and lactate to 200,µM for acetate and glycerol. The MS2 ion-trap spectra obtained at pH 7 (ammonium acetate buffer) were used to distinguish maleate (cis -2-butenedioic), which gave [M,CO2,H], (m/z 71), from fumarate (trans -2-butenedioic), which showed first a loss of water yielding an instable peak at m/z 97. The compounds involved in the aerobic-anaerobic adjustment of the metabolism were revealed by linear discriminant analysis. Acetate, citrate, glucose, maleate (which decreased during the daytime), and particularly succinate (which increased), showed the maximal discrimination power between the day- and night-time samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||